The hormonal theory of the origin of freemartins has been the basis for much research on sex differentiation and intersexuality. However, the agents responsible for the etiology and the subsequent development and variation of the freemartin syndrome have not been elucidated. It is proposed that the experimental induction of freemartinism in the sheep, a species in which the syndrome occurs only rarely, will make possible the isolation of the inductor substance. Attempts to determine the critical period for freemartin induction will be made by utilizing intrauterine surgery to experimentally induce choriovascular anastomosis between adjacent fetuses in unilaterally-ovariectomized superovulated ewes. Subsequently, it will be determined whether the factors responsible for induction are present in the adult as well as in the fetal circulatory system, and whether they are located in the cellular or non-cellular fractions of the blood. This will be accomplished via vascular infusion of these components into the developing fetus. It is anticipated that this work will lead to the isolation of the factor or factors directly responsible for freemartin etiology.